Why we need a noninvasive diagnostic test for minimal to mild endometriosis with a high sensitivity.
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Adolescent↗
Biomedical subjects
T M D'Hooghe
Publications and source records attributed to T M D'Hooghe.
Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon.
BACKGROUND: Inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-alpha), are important in the pathogenesis of endometriosis. We assessed the efficacy of anti-TNF monoclonal antibody (mAb, c5N), known to prevent induced endometriosis in baboons, in reducing established endometriosis in baboons. METHODS: This prospective, randomized, blinded, controlled study was conducted in baboons at the Institute of Primate Research (IPR), Nairobi, Kenya. Endometriosis was induced in 18 adult female baboons (Papio anubis) with regular menstrual cycles and a normal pelvis; the extent of endometriosis was documented by videolaparoscopy 25 days later. The baboons were then randomly assigned to receive a single infusion of either placebo (n=7, 5 ml/kg) or c5N (n=11, 5 mg/kg). Follow-up laparoscopy was performed 25 days later to document any differences in the number, surface area and estimated volume of lesions between the two groups and between the first and the second laparoscopies in each group. Representative biopsies of at least one endometriotic lesion per baboon were obtained at the final laparoscopy. RESULTS: Significant reductions in total surface area, estimated total volume of endometriotic lesions and both number and surface area of red lesions were observed after treatment with c5N, but not after placebo treatment, when compared to the initial laparoscopy. Conversely, a significant increase in the number of typical and red lesions was observed after placebo treatment when compared to the initial laparoscopy. Neither c5N nor placebo treatment affected the menstrual cycle. CONCLUSION: In baboons with induced endometriosis, anti-TNF-mAb (c5N) treatment significantly reduced the extent of endometriosis, mainly due to reducing both the number and surface area of red lesions. These findings suggest that anti-TNF-mAb therapy may have therapeutic potential for active peritoneal endometriosis.
Animals↗
Endometriosis, recurrent miscarriage and implantation failure: is there an immunological link?
Endometriosis is more frequently diagnosed in patients with infertility than in a normal population. The goal of this paper is to give an overview of the clinical and fundamental evidence for a possible link between endometriosis and (recurrent) miscarriage or implantation failure after treatment with assisted reproductive technology. According to the literature, there is insufficient evidence for an association between endometriosis and (recurrent) miscarriage, but there is, however, epidemiological evidence to support the link between endometriosis and recurrent implantation failure after assisted reproduction. This can possibly be explained by alterations in humoral and cell-mediated immunity in women with endometriosis. Humoral immunological changes include increased formation of antibodies against endometrial antigens, anti-laminin-1 auto-antibodies and other auto-immune antibodies (e.g. antiphospholipid). Cell-mediated immunological changes include alterations in peritoneal and follicular fluid immune cells and cytokines. The possible negative effect of these immunological changes on folliculogenesis, ovulation, oocyte quality, early embryonic development and implantation in women with endometriosis suggests that infertility in endometriosis patients may be related to alterations within the follicle or oocyte, resulting in embryos with decreased ability to implant.
Abortion, Habitual↗
The effect of endometriosis, cycle stage, lymphocyte suppression and pregnancy on CA-125 levels in peritoneal fluid and serum in baboons.
BACKGROUND: Serum CA-125 during the mid-follicular phase has been reported to be a clinically useful and reproducible marker in the diagnosis of advanced endometriosis in women. This study was undertaken to document the effect of the menstrual cycle, pregnancy and lymphocyte suppression on CA-125 levels in peritoneal fluid (PF) and serum in baboons with a normal pelvis and baboons with endometriosis. METHODS: CA-125 levels were measured in 264 serum samples that were serially obtained during one menstrual cycle from 10 animals with and without endometriosis. In addition, CA-125 levels were determined in 204 archived samples (serum, n = 112 and PF, n = 92) obtained from 32 female baboons with or without endometriosis. The CA-125 assays were performed by radioimmunoassay using kits from Centocor (Malvern, PA, USA). RESULTS: Serum CA-125 levels were at their highest during menstruation and decreased progressively during the follicular and luteal phase. PF CA-125 levels were increased during the follicular phase in baboons with a normal pelvis, but no cyclic changes were observed in animals with endometriosis. Serum CA-125 levels were unaffected by induction, lymphocyte suppression or pregnancy. Induction of endometriosis resulted in increased PF CA-125 levels, whereas lymphocyte suppression or pregnancy had no effect. CONCLUSION: In baboons, serum CA-125 originates mainly from eutopic endometrium whereas the main source of PF CA-125 seems to be the peritoneum or ectopic endometrium. The baboon appears to be a valid model to further study the relationship between endometriosis and CA-125.
Animals↗
Endometriosis and subfertility treatment: a review.
The aim of this article is to present a review on the influence of endometriosis on assisted reproductive techniques (ART), as well as on the influence of ART on endometriosis. Based on recent literature, this article will try to answer the following questions: 1) Does endometriosis change the success rate of ovulation induction (OI), intrauterine insemination (IUI) and in vitro fertilisation (IVF) and does previous chirurgical treatment of endometriosis change the success rate of OI, IUI and IVF? 2) Do ART alter the course of the disease? In order to answer these questions, we based ourselves on the following recent guidelines and reviews by reknown experts on endometriosis: the ESHRE Guideline for the Diagnosis and Treatment of Endometriosis, The Practice Committee of the American Society for Reproductive Medicine: Endometriosis and Fertility; a recent review paper on the relationship between endometriosis and subfertility and a recent meta-analysis on the relationship between endometriosis and ART. This review was then completed using more recent papers, published on PubMed as well as background articles, important references and own research papers presented at international meetings. The pregnancy rate after OI, IUI and IVF is decreased in women with endometriosis when compared to controls. The effect of previous surgery for endometriosis is unclear, due to great lack of standardised studies using well defined operation techniques and patient groups. The effect of ART on the spontaneous evolution and recurrence rate of endometriosis has hardly been studied. The presence of endometriosis has a negative effect on the pregnancy rate after ART. It is unclear if surgical treatment prior to ART may increase the pregnancy rate after ART. It is also unclear if ART is a risk factor for recurrence/progression of endometriosis.
Endometriosis↗
The prevalence of endometriosis among African-American and African-indigenous women.
Endometriosis is gynaecological disorder, characterized by the growth of endometrial tissue outside the uterine cavity. It is the most common cause of pelvic pain and occurs in 20-25% of women with infertility. Although Sampson first described endometriosis in 1927, studies on the prevalence of endometriosis among African women are still lacking. The current thinking is that endometriosis rarely affects women from the African origin. However, in African-American women in the USA, endometriosis is one of the commonest indications for major gynaecological surgery and hysterectomy, and is associated with long hospital stay and high hospital charges. There is also some evidence that endometriosis is more commonly found in African-American patients from private practice than in African-American patients treated in public hospitals. The prevalence of endometriosis in African-indigenous women with infertility seems low, possibly due to a different life style (early pregnancy, increased risk for PID and blocked Fallopian tubes) and due to lack of laparascopic facilities and specific training of African gynecologists to diagnose ascites caused by endometriosis appear to be more frequently observed in African-indigenous of African-American women than in women with other ethnic backgrounds.
Black or African American↗
Baboon model for fundamental and preclinical research in endometriosis.
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Animals↗
Quantitative assessment of endometrial-peritoneal interaction in vitro: a non-invasive diagnostic test for women with endometriosis?
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Cell Adhesion↗
The Baboon as a Nonhuman Primate Model for the Study of Human Reproduction.
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Animals↗
Invisible microscopic endometriosis: how wrong is the sampson hypothesis of retrograde menstruation to explain the pathogenesis of endometriosis?
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Ascitic Fluid↗
Immunobiology of the reproductive tract in a female baboon.
The aim of this study was to assess the suitability of various antihuman antibodies directed against immunocomponent cells to identify components involved in cellular and humoral immune responses in the immune organs of a female baboon, and to use these reagents to analyze the immunobiology of its reproductive tract. A female baboon of reproductive age was euthanized in the luteal phase of the menstrual cycle, and samples of spleen, intestines, tonsil, lymph nodes, Fallopian tube, uterus, cervix, and vagina were removed. Tissues were either fixed in 10% unbuffered formaldehyde, Bouin's fluid, or 95% ethanol containing 5% glacial acetic acid, and embedded in paraffin, or frozen unfixed. Frozen sections were then fixed in 100% acetone. Subsequently, tissue sections were reacted with the following antihuman antibodies directed against CD3, CD45RA, CD45RO, CD4, CD8, CD20, CD68, HLA-DR, CD57, CD103, CD15, and TIA-1: IgA, IgG, IgM, J-chain, secretory component, and neutrophil elastase, using routine immunohistology techniques. Human tissues (spleen, small intestine, lymph node, and tonsil) were used as positive controls. All antihuman antibodies crossreacted with baboon tissues, except neutrophil elastase, CD15, CD45RO, CD57, and CD1A. The distribution of immune cells in the reproductive tract of the female baboon was comparable to that in the human and offers the potential for this primate to be used as a model for the study of human reproductive immunology.
Animals↗
Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis.
In a preliminary study the hypothesis was tested that cytokine profiles in peripheral blood were higher in women with deep infiltrating endometriosis and cytokine profiles in peritoneal fluid were higher in women with superficial endometriosis. Thirteen women of reproductive age having laparoscopy for infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-10 (IL-10), Transforming Growth Factor-betal (TGFbeta1), and Interferon-gamma (IFN-gamma). No significant cytokine differences were observed in either peritoneal fluid or peripheral blood between IL-6, TGFbeta1, IFNgamma, TNF-alpha and IL-10 of women with superficial endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6). The results of this preliminary study do not show significant differences in peripheral blood and peritoneal fluid cytokine levels between women with deep infiltrating endometriosis compared to women with superficial disease. Future studies with increased sample size are required to either confirm or refute these preliminary findings.
Adult↗
Effect of menstruation and intrapelvic injection of endometrium on inflammatory parameters of peritoneal fluid in the baboon (Papio anubis and Papio cynocephalus).
OBJECTIVE: Our purpose was to test the hypothesis that menstruation and intrapelvic injection of endometrium for the induction of endometriosis affect inflammatory parameters in peritoneal fluid from baboons. STUDY DESIGN: In the first part of this study, 107 laparoscopies were performed in 62 female baboons with a normal pelvis during menstruation, the follicular phase, and the luteal phase. In the second part of this study, 21 baboons were studied during paired laparoscopies in the follicular phase and the luteal phase of the cycle. In the third part of this study, 11 baboons were studied by paired laparoscopies during menses and during the nonmenstrual phase of the cycle. In the fourth part of this study, paired laparoscopies were performed in 7 baboons before and after intrapelvic injection of endometrium. Peritoneal fluid was aspirated and measured in all laparoscopies and assessed for leukocyte concentration. In the third and fourth parts of the study, peritoneal fluid was analyzed for the concentrations of inflammatory cytokines and for the proportions of cells with immunohistochemical staining positive for these cytokines. RESULTS: During menstruation, in comparison with nonmenstrual phases of the cycle, the leukocyte concentration of the peritoneal fluid was increased significantly, as were the proportions of peritoneal fluid cells with positive staining for tumor necrosis factor alpha, transforming growth factor beta(1), and intercellular adhesion molecule 1 and the peritoneal fluid concentrations of transforming growth factor beta(1) and interleukin 6. After intrapelvic injection of endometrium, the peritoneal fluid leukocyte concentration and the proportions of peritoneal fluid cells with positive staining for tumor necrosis factor alpha, transforming growth factor beta(1), CD3, and human leukocyte antigen (DR locus) significantly increased. CONCLUSION: Subclinical peritoneal inflammation occurs in baboons during menstruation and after intrapelvic injection of endometrium.
Animals↗
Increased frequency of chromosomal abnormalities in female partners of couples undergoing in vitro fertilization or intracytoplasmic sperm injection.
OBJECTIVE: To determine the prevalence of chromosomal abnormalities in female partners of couples undergoing IVF or intracytoplasmic sperm injection (ICSI). DESIGN: Prospective study. SETTING: Leuven University Fertility Center. PATIENT(S): Female candidates for IVF or ICSI. INTERVENTION(S): An initial cytogenetic study was performed on peripheral blood lymphocyte cultures using G- and R-banding. In all patients, > or =25 metaphases were examined. If a chromosomal aberration was detected, additional cytogenetic studies were performed for precise identification. MAIN OUTCOME MEASURE(S): Abnormal female karyotypes in comparison with the general female population. RESULT(S): Cytogenetic analysis was performed in 263 female partners of couples before entering an IVF or ICSI program. The prevalence of autosomal reciprocal balanced translocations was seven times higher in the study group (1.14%) than in the general population (0.16%). All abnormal karyotypes were found in the IVF group with male factor infertility. CONCLUSION(S): Chromosomal abnormalities are more frequent in the female partners of couples seeking fertility treatment. We recommend chromosomal analysis in women before starting IVF or ICSI treatment, even in the presence of male factor infertility.
Adult↗
Endometriosis and recurrent pregnancy loss.
A possible association between endometriosis and spontaneous abortion has been suggested in mostly uncontrolled and/or retrospective studies. Some controlled studies evaluating the association between endometriosis and spontaneous abortion showed important methodological shortcomings: heterogeneity between cases and controls, analysis of the abortion rate before the diagnosis of endometriosis, and selection bias of study and control groups. On the basis of controlled prospective studies, there is no evidence that endometriosis is associated with (recurrent) pregnancy loss or that medical or surgical treatment of endometriosis reduces the spontaneous abortion rate. In programs of assisted reproduction, some studies have shown that the number and quality of oocytes, the fertilization rate, and the implantation rate per embryo may be reduced in women with endometriosis, but this observation has not been confirmed by other investigators. Future studies evaluating the reproductive outcome of patients with endometriosis in assisted reproduction programs should include reliable information about the date and histological confirmation of the diagnosis of endometriosis, time interval between treatment with assisted reproduction and the last laparoscopy, possible recurrence of endometriosis, effectiveness of interim hormonal (suppressive) therapy, accuracy of ultrasound diagnosis, and accuracy of "negative" diagnosis.
Abortion, Habitual↗
Pelvic inflammation induced by diagnostic laparoscopy in baboons.
OBJECTIVE: To test the hypothesis that diagnostic laparoscopy can cause pelviperitoneal inflammation. DESIGN: Retrospective analysis of data collected during a prospective controlled study in baboons. SETTING: An academic research environment. ANIMAL(S): Samples were collected during laparoscopies in female baboons at the Institute of Primate Research, Kenya. INTERVENTION(S): In the first part of the study, 44 laparoscopies were performed in 16 baboons (5 with a normal pelvis, 11 with endometriosis) during the luteal phase, with a time interval of 1 month. In the second part of the study, 53 laparoscopies were performed in 15 baboons (6 with a normal pelvis, 9 with endometriosis) during the late follicular and luteal phases of one cycle, with a median time of 3-4 days between each laparoscopy. MAIN OUTCOME MEASURE(S): Peritoneal fluid (PF) was measured and analyzed for white blood cell (WBC) concentrations and, in the second part of the study, for the distribution of lymphocyte subsets (CD3, CD4, CD8, and CD20) and for the presence of cytokines transforming growth factor-beta1, interleukin (IL)-6, and IL-10. RESULT(S): In the first part of the study, PF volumes and WBC concentrations were comparable at the baseline and follow-up laparoscopies. In the second part of the study, PF obtained at the second laparoscopy showed a 10-fold increase in volume, a 3-fold increase in WBC concentration, a 10-fold increase in IL-6 concentration, and a 2-fold increase in transforming growth factor-beta1 concentration when compared with PF obtained at the first laparoscopy. The PF subset of granulocytes and CD3-positive cells was higher and the PF subset of macrophages was lower at follow-up laparoscopies than at the baseline laparoscopy. CONCLUSION(S): Diagnostic laparoscopy can cause peritoneal inflammation in baboons.
Analysis of Variance↗
Ultrasound covers and sonographic gels are embryo-toxic and could be replaced by non-toxic polyethylene bags and paraffin oil.
The objective of this study was to test the hypothesis that ultrasound covers and sonographic gels, used during vaginal ultrasound, are toxic for mouse embryonic development in vitro. A prospective randomized design was used on pronucleate ova of F1 hybrid CBA x C57Bl female mice. The mice were superovulated with pregnant mare's serum gonadotrophin and human chorionic gonadotrophin and mated with CBA x C57Bl males. The pronucleate ova were randomly divided between culture media with the addition of commercially available ultrasound covers and sonographic gels in different concentrations. As controls and potential alternatives, plastic polyethylene bags and paraffin oil were tested simultaneously. Embryo-toxicity was assessed by documenting cleavage capacity, blastocyst formation and embryo degeneration in vitro. Exposure of culture medium to the ultrasound covers and sonographic gels tested resulted in a severely reduced cleavage capacity, a high incidence of embryo degeneration and absent or impaired blastocyst formation. This toxic effect could be reduced by high dilutions in vitro. In contrast, plastic polyethylene bags and paraffin oil had no influence on in-vitro development of mouse ova. We conclude that commercially available ultrasound latex covers and sonographic gels are toxic for mouse embryos and can potentially influence embryonic development during infertility treatment. It is safer to perform vaginal ultrasonic measurements using non-toxic paraffin oil (as contact fluid) and plastic polyethylene bags (as ultrasonic cover).
Animals↗
The effect of pregnancy on endometriosis in baboons (Papio anubis, Papio cynocephalus).
BACKGROUND: This study was performed to test the hypothesis that endometriosis undergoes regression during pregnancy. METHODS: This study was performed on 11 baboons with histologically proven endometriosis, housed at the Institute of Primate Research, Nairobi, Kenya. In each individual baboon paired laparoscopies were performed prior to and during pregnancy (6 during first and 5 during second trimester of gestation) with an interval of 5 +/- 3 months. During each laparoscopy the number, size and type of endometriosis implants were noted in detail on a pelvic map; the endometriosis score and stage were calculated according to the revised American Fertility Society (AFS) classification. In each baboon the observations prior to and during pregnancy were compared and analysed by Wilcoxon signed rank test (two-tailed). RESULTS: No significant change was observed in the AFS score or stage of endometriosis, or in the number, size and type of endometriotic lesions in baboons during gestation when compared to the nonpregnant state. CONCLUSION: In baboons pregnancy had no significant effect on endometriosis during the first or second trimester of gestation.
Animals↗